The disclosed subject matter relates to devices and methods for determining molecular structure. Atomic force microscopy provides for imaging utilizing measurements of force between a probe and the surface of an object to be imaged. When the stylus is brought into contact with the surface, it can become deflected by forces in accordance with Hooke's Law. This deflection can be measured and recorded, such that the atomic force microscope can produce a 3-D surface map of the object under inspection.
Scanning probe microscopes (SPMs), for example, atomic force microscopes, can allow imaging and chemical characterization of surface down to the atomic scale. The localized tip-sample interactions in SPMs limit high resolution images to the topmost atomic layer of surface. Consequently, characterizing the 3-D inner structure of materials and biomolecules can be difficult for SPMs.
Scanning probe microscopes (SPM) can be operated in so-called tapping mode, where the probe or stylus comes into intermittent contact with the surface to be imaged. Operation in tapping mode can avoid causing damage and prevent the probe from sticking to the surface, while ensuring that the probe is close enough to the surface to produce high quality images. The probe can be capable of not only physically imaging the sample but identifying its biochemical composition.
However, using a probe to obtain information about the chemical identities of atoms and molecules on the Angstrom scale can necessitate imaging modalities that operate under vacuum, which can be ill-suited for biomolecules in a solution. Accordingly, there exists a need for an improved imaging technique for determining molecular structure.